2-Acetylaminofluorene mechanistic data and risk assessment: DNA reactivity, enhanced cell proliferation and tumor initiation

Abstract

The aromatic amine 2-acetylaminofluorene (AAF) produced neoplasms in diverse target organs of many animal species. AAF was DNA-reactive after N-hydroxylation by CYP1A2 in the liver and nitrenium ion formation at the target site. In mouse bladder, AAF-DNA adducts were proportional to dose. An epigenetic component for tumor formation was also present since tumor incidence and hyperplasia showed a threshold dose and decreased following discontinuation of AAF exposure. In contrast, both adduct and tumor formation in the liver were proportional to dose, and discontinuation of AAF did not reduce tumor incidence.